The overall objective of this project is to characterize the processes involved in inactivation of norepinephrine (NE) in vascular tissue and to determine the relationships which exist among these processes. The experiments will be performed on the adventitia (which contains the adrenergic nerve terminals) and the media (which contains the smooth muscle cells) of rabbit aorta. During the coming year I hope to complete the development of model systems for studying the neuronal and extraneuronal transport systems for NE. To study these transport systems it is necessary to prevent the removal of NE from the cytoplasm after it is transported into the cell. Experiments with several monoamine oxidase and catechol-0-methyl transferase inhibitors will be completed. A pretreatment schedule which blocks NE metabolism without affecting uptake will be selected. Experiments will also be performed with reserpine to block storage of NE in nerve granules without affecting uptake by the membrane transport systems. Tissue pretreated in this manner will then be used to study the kinetics of NE uptake by the adventitia and media and the substrate specificity and effect of drugs on these uptake processes.